DESCRIPTION (provided by investigator): The incidence of sudden cardiac death in the United States ranges from 200,000 to 450,000 annually, and approximately 50 percent of all cardiovascular disease deaths are sudden and unexpected.1 The implantable cardioverter defibrillator (ICD) has demonstrated its efficacy over pharmacotherapy in reducing mortality related to potentially lethal ventricular arrhythmias.2-4 Cardiac autonomic control plays a critical role in ventricular fibrillation and mortality.5 Improving cardiac autonomic control by enhancing parasympathetic activity and regulation is known to be protective against ventricular arrhythmias and sudden death.6 Exercise training interventions among healthy and cardiac populations have improved parasympathetic activity.7,8 However, to date, there have been few intervention studies that have examined the effect of exercise on parasympathetic activity and regulation, and none specifically among ICD patients. This application will test the feasibility, acceptability, and short-term efficacy of a 3-month supervised exercise intervention, designed specifically for ICD patients, with the primary aim of enhancing parasympathetic activity and estimating an effect size. Therefore, we propose a preliminary randomized, controlled clinical trial to compare the efficacy of a 3-month supervised exercise intervention to an education-based contact control group [among a sample ICD patients for secondary prevention] (N=30). The exercise intervention will be personalized according to each participant's exercise tolerance and ICD programmed settings (e.g., heart rate cut-off) and will include low impact aerobic activity performed at moderate intensity. This project utilizes a randomized, repeated measures design consisting of assessments at baseline, 3-months, and 6-months. This application builds upon prior work in several innovative ways: (1) examining the direct effects of exercise on parasympathetic function in ICD patients, (2) the inclusion of secondary endpoints of arrhythmia and shock occurrence frequencies, and (3) parasympathetic function will be examined in relation to changes in exercise tolerance as well as changes in psychological well-being and quality of life from pre- to post-exercise intervention, and short-term follow-up. The data obtained from this R21 will provide effect size estimates that will support the submission of a larger randomized clinical trial designed to test the efficacy of exercise conditioning on parasympathetic activity indices. It is the first study that we know of to examine the direct effects of exercise on parasympathetic activity and regulation among a sample of ICD participants. If exercise improves parasympathetic activity and regulation, then it may reduce the frequency of ventricular arrhythmias and sudden death. If we can document this relationship, we may be able to reduce the need for ICDs or find a better stratification method for patients that may currently meet a certain criterion for ICD implantation. Patients eligible for ICDs are a diverse group, and this proposed pathway may only be true for some individuals. This trial may help to revise treatment approaches for patients at risk for arrhythmias and sudden cardiac death. PUBLIC HEALTH RELEVANCE: From 1990 to 2002, there were 415,780 ICDs implanted in the United States alone.9 If we are able to help find an appropriate clinical intervention that reduces potentially lethal arrhythmias and sudden death then we may reduce the need for ICDs and/or improve quality of life in those that have ICDs. Improved treatment or stratification approaches could distinguish a select subgroup of patients who may truly benefit from an ICD, and subsequently, have a huge impact on public health and reduce health care costs, as well as continuing to maintain and improve QOL of the patients;thus, there are several positive implications for the patient, health care, and the community.